tbuckley/cabot-search huggingface dataset:
How to close the care gap: Factors hindering the use of BRCA mutation profiling of patients with breast cancer and ovarian cancer in a real world setting.
Authors: Muneer V. A., Dilip V. Harindran Vallathol, Uma V. Sankar, Narayanankutty Edavalath Warrier, Sreedharan P. S., Sajeevan K. V., Prasanth V. Parameswaran, Gopika V P
Journal: Journal of Clinical Oncology (2023)

e18636 Background: The majority of hereditary breast and ovarian cancers are linked to BRCA1/2 mutations. However, in patients with a suggestive personal or family history, a specific predisposing gene is identified in &lt; 30% of cases. Mutation testing is recommended for individual genes in the appropriate clinical setting with a high suspicion index for a specific mutated gene. The risk of contralateral breast cancer increases with the time since the first breast cancer, reaching 20%–30% at ten years of follow-up and 40%–50% at 20 years, depending on the gene involved. Methods: The study assessed the prevalence of BRCA testing among young breast cancer women (age less than 50 years) and explored the factors hindering the performance of the BRCA mutation test. Among the 3400 breast cancers reported from 2017 to 2022, 46.17% (n = 1570) of young breast cancer women were advised for BRCA testing. We administered the questionnaire on factors influencing the BRCA mutation profiling performance to all the young breast cancer women (n = 1532). The data was collected from the electronic medical records and the department of molecular oncology. We performed regression analysis to predict the act of BRCA mutation profile testing. Results: Among them (n = 1570), only 17.70% (n = 278) performed BRCA1/2 genetic testing. In 278 patients who had undergone BRCA testing, pathogenic or likely pathogenic BRCA1/2/HRR mutations were detected in 52 patients (18.7%). 38 (13.7%) with BRCA 1, 14(5%) with BRCA2. Somatic with HRR testing was done in 13(4.6%), Somatic testing in 37(13.3%) and germline testing was done in 228 (82%). BRCA mutation was detected in 18 (34.6%) patients with breast cancer, 32(61.5%) patients with ovarian cancer. The factors influencing not performing the BRCA testing were the higher Cost of the test (83.4%), delay in getting the result (32.4%), unawareness of the importance of the test (52.6%), and not being advised by the physician as a mandatory test to perform (47.6%) and male spouse as a decision maker (31.8%). Conclusions: BRCA mutation profile test is mandatory to know their recurrence risk and treatment decisions for opting for PARP inhibitor. But the Cost of the test is the main barrier to performing this in a low-middle-income country setting. Female gender and related decision-making conflict could be the other reasons not to perform the test.
Role of ketogenic diet in the management of cancer: A systematic review.
Authors: Nikhila Chelikam, Urvish Patel, Sai Anusha Akella, Abdirazak Ali, Manisha Rakesh Lakhanpal, Aryak Singh, Varneet Toor, Prashanth Gumpu Shivashankar, Shlok Vimal Shah, Simmy Lahori, Lokesh Manjani, Rahul Gujarathi, Divesh Manjani, Avinash Adiga, Geetika Kukreja
Journal: Journal of Clinical Oncology (2023)

e24042 Background: Cancer is 2nd leading cause of death (1 in every 5) in the United States followed by heart disease. Use of ketogenic diet (KD)- high-fat &amp; low-carbohydrate diet, allows fatty acids to become the obligatory source of cellular energy which can help in decreasing the tumor cell growth. Aim of this study was to evaluate role of KD in different types of cancer. Methods: We performed a systematic review using PRISMA protocol to identify articles describing the role of the ketogenic diet in cancer patients in PubMed. Keywords like cancer, neoplasm, tumor, KD, and intermittent fasting (IF) were used &amp; filters like full text, English, human, observational studies, &amp; clinical trials (CTs) were applied between 2018-2022. Results: Of the 362 studies after using filters only 22 studies were CTs. Of these 22, 12 studies were excluded &amp; 10 studies were included in this study. [Table 1] We found CTs describing role of KD, IF or standard diet (SD) in brain cancer, non-metastasized rectal cancer, high-grade glioma, head and neck squamous cell carcinoma, locally advanced and metastatic breast cancer, ovarian and endometrial cancer. KD was describes as an accompanying measure for patients undergoing standard-of-care therapy that helps to improve the quality of life, survival &amp; acceptable safety and tolerability. KD may augment the antitumor effects of classic chemotherapy and radiotherapy. Conclusions: Role of KD is described in depth, but majority RCT results were heterogeneous in nature to provide quantitative measures of survival timeline, outcomes, &amp; recovery. Thus, more human prospective studies are warranted to evaluate the therapeutic effectiveness &amp; safety of KD.[Table: see text]
Creating an infrastructure to address physician and advanced practice provider burnout at a complex community cancer care delivery system.
Authors: Alison Tray, Mary Kate Eanniello, Peter Paul Yu
Journal: Journal of Clinical Oncology (2023)

11015 Background: Oncology clinicians are at risk for developing burnout due to work-related factors such as high acuity patients, long work hours, limited autonomy, administrative and documentation demands (Copur, 2019; Eelen et al, 2014). The COVID-19 Pandemic has intensified burnout due to rapid and multiple changes in clinical practice, lack of fulfillment, and heightened moral distress and personal challenges (Hlubocky et al 2021). As a multi-center community cancer care system, an infrastructure was created and operationalized to address the work-related factors contributing to burnout. The purpose of the project was improved identification and prioritization of clinician (physician and APP) needs with subsequent targeted intervention. Methods: To measure success, a partnership with the American Medical Association (AMA) was formed to deploy the Mini-Z burnout survey. The survey was administered on July 2-August 20, 2021 to all Medical Oncology physicians and Advanced Practice Providers (APPs), n = 60. The survey was re-deployed from July 13-September 2nd, 2022. Data was collated by the AMA and presented back to executive leadership. Through this survey and follow up focus groups, it was identified that physicians tended to struggle more with the EHR and inability to disconnect from work compared to APPs. Our APPs identified several areas of opportunity including onboarding/orientation, mentorship/professional development, pay and scope of practice. An EHR Well-being Committee was established to evaluate EPIC signal reports to address both system and individual clinician needs. To address APP needs, key factors were addressed in the realm of professional development/orientation, compensation and scope of practice. This was approached with the goal of short-term gains and long-term sustainability. Results: The results indicated a 23.8% improvement in job satisfaction, 4.9% improvement in job stress, and 26.3% improvement in employment outlook. A decrease was also noted in EHR Time outside of work (4.5%) and burnout (16.1%). All areas of improvement met or exceeded national benchmarks. Analysis of these results indicate statistical significance for job satisfaction (p = 0.028, CI 2.8-40.4%) and employment outlook (p = 0.033, CI2.4-45.8%). Results that indicated improvement but were not statistically significant were job stress (p = 0.688, CI 17.6-27.4%), burnout (p = 0.191, CI 7.4-37.5%) and EHR time outside of work (p = 0.806). Conclusions: While the survey data does not account for clinician turnover between 2021 and 2022, initial review indicates a positive impact on job satisfaction and employment outlook which may be an early indication of improved colleague appreciation. Further study, post-pandemic is needed to evaluate effectiveness of care team efficiency and ongoing work to streamline EHR usage.
Long-term survival following adrenalectomy for secondary adrenal tumor (SATs): A systematic literature review and meta-analysis.
Authors: Abdulrahman Ahmad Alhajahjeh, Joshua Kong, Tanya Odisho, Hannan Ahmad Maqsood, Bayan A Al-Share, Awni Shahait, Mohammed Shahait
Journal: Journal of Clinical Oncology (2023)

e21181 Background: Secondary Adrenal tumors (SATs) are uncommon forms of cancer that occur as a result of metastasis from primary tumors (PT) elsewhere. A systemic review and metanalysis was conducted to assess characteristics and survival following adrenalectomy for SATs. Methods: A systematic literature search was performed (01/1990-12/2022) using several databases (PubMed, Embase, the Cochrane Library, the ASCO library). The inclusion criteria included a known previous PT and confirmed isolated adrenal metastasis either by biopsy or serial imaging (synchronous or metachronous) in patients who underwent adrenalectomy. The primary outcome of interest was the overall survival (OS) of patients following adrenalectomy of SAT. Metanalysis of pooled survival curves for OS was completed, and KM curves were used to create pseudo-individual patient data. Results: A total of 29 studies were analyzed, including 2,401 patients with SAT most of which underwent adrenalectomy. The average age of the group was 60.8 ±3.54years. Lung cancer was the most common PT (33.3%), followed by renal cancer (24.7%). About two thirds (67.7%) of patients had isolated metastasis. The average time from PT diagnosis to adrenal metastasis was 22.4 ±11.11 months. Data of 1,712 patients were used to estimate the combined 5-year OS. The median OS was 35.7 months [95% Confidence interval (CI): 29.1 - 50.4]. One, three, and five-year OS were 80.9% [95% CI: 75.6 - 84.6], 49.6% [95% CI: 43.4 - 56.8], and 38.2% [95% CI: 32.2 - 44.5], respectively. Conclusions: The results of this metanalysis and systematic literature review provide insight into the long-term survival of patients with secondary adrenal tumors who underwent adrenalectomy. The study highlights the need for further research to identify the risk factors that play a role in the clinical outcome of adrenalectomy in patients with adrenal metastasis.
Platelet decline rate as the indication of using recombinant human thrombopoietin to prevent chemotherapy induced thrombocytopenia: A prospective, randomized, controlled study.
Authors: Zhongliang Wang, Ting Ye, Li Fan, Jieying Zhang, Rubo Cao, Yanshen Liu, Ling Peng, Jing Chen
Journal: Journal of Clinical Oncology (2023)

e24171 Background: Doxorubicin combined with ifosfamide is the common regimen for patients with sarcoma, which will induce severe thrombocytopenia. Sarcoma patients especially those with rapid platelet count decline after receiving this regimen could not avoid severe thrombocytopenia, even Recombinant Human Thrombopoietin(rhTPO) was used when the platelet count decreased to 75,000/μL according to current guidelines. The present study aimed to test the efficiency and safety of using rhTPO to prevent severe thrombocytopenia when rapid platelet count decline occurred. Methods: Our previous data showed those patients with rapid platelet count decline more than 40% within 3 days after administration of doxorubicin combined with ifosfamide were more likely to develop severe thrombocytopenia. In this prospective study, 53 patients with this characteristic were randomly assigned to prevention group (starting rhTPO immediately after enrollment) or treatment group (starting rhTPO when platelet count was less than 75,000/μL after chemotherapy). rhTPO was administrated with 300IU/kg·d until the platelet count increased to 100,000/μL or by 50,000/μL. Incidence and duration of grade 3 to 4 thrombocytopenia, proportion of platelet transfusion and adverse reactions were collected and analyzed. Results: The incidence of grade 3 to 4 thrombocytopenia in the prevention group and the treatment group was 63% and 81% respectively (p = 0.224), however the incidence of grade 4 thrombocytopenia in the former was significantly lower than that in the latter(22% versus 50% , p = 0.047).The duration of grade 3 to 4 thrombocytopenia in the prevention group had a declining trend compared with the treatment group( 2.6±2.8d versus 3.7±3.3d, p = 0.198). There was no difference in the proportion of platelet transfusion between the two groups. No rhTPO related toxicities of grade 3 to 4 were observed in both groups. Conclusions: For sarcoma patients treated with doxorubicin combined with ifosfamide, rapid platelet count decline more than 40% within 3 days after chemotherapy can be used as an indicator for the prophylactic administration of rhTPO, which can significantly reduce the probability of grade 4 thrombocytopenia without increasing toxicity. Clinical trial information: ChiCTR1900022667 .
Longitudinal associations between peripheral neuropathy and neurocognitive decline in long-term survivors of pediatric cancer treated without central nervous system (CNS) directed therapy.
Authors: AnnaLynn Williams, Nicholas Steve Phillips, Chelsea Goodliffe Goodenough, Tara M. Brinkman, Chiara Papini, Lisa M Jacola, Angela Delaney, Gregory T. Armstrong, John L. Jefferies, Raja B. Khan, Leslie L. Robison, Melissa M. Hudson, Kirsten K. Ness, Kevin R. Krull
Journal: Journal of Clinical Oncology (2023)

10054 Background: Survivors of pediatric cancer treated without CNS-directed therapy are at risk of neurocognitive impairment and peripheral neuropathies. Using the St. Jude Lifetime Cohort, we investigated longitudinal associations with neuropathy to inform contributors to long-term cancer-related neurocognitive decline. Methods: Survivors of pediatric cancer (N=899 mean age 32 [SD 12], 24[10] years from diagnosis) treated without CNS-directed therapy completed neurocognitive testing and medical assessments at two timepoints (T1, T2 4.4[2.3] years apart). Peripheral sensory and motor neuropathy subscales combined with functional tasks were severity graded using a modified CTCAE (no neuropathy = none or grade 1 at T1 and T2; new onset = new grade 2 or 3 at T2; persistent = grade 2 or 3 at T1 &amp; T2). Linear regression models estimated change in neurocognitive Z-score associated with neuropathy groups, adjusted for diagnosis age, time between visits, sex, race/ethnicity, high-dose intravenous methotrexate &amp; baseline neurocognitive Z-score. Results: New onset sensory (n=33, 3.6%) and motor (n=35, 3.9%) neuropathy was associated with a 0.33 standard deviation (SD) decline in visual-motor processing speed (Table). New onset motor neuropathy was associated with a 0.50 SD decline in sustained attention as well as significant declines in verbal recall, working memory, and cognitive flexibility (p’s&lt;0.05). Persistent sensory neuropathy (n=25, 2.8%) was associated with large declines in focused attention and cognitive flexibility (p’s&lt;0.05). Persistent motor neuropathy (n=18, 2.0%) was associated with a 0.50 SD decline in sustained attention, verbal recall, and working memory (p’s&lt;0.05). Conclusions: Peripheral neuropathies are associated with future neurocognitive decline in adult survivors of pediatric cancer. Research is needed to understand shared mechanisms (e.g. pain, inflammation) to inform targeted interventions to improve neuropathic symptoms and neurocognitive function. [Table: see text]
Timing of specialized palliative care integration and its impact on quality of end-of-life care indicators among Latin American cancer patients.
Authors: Douglas Dias e Silva, Vanessa Melo Ferreira, Diego Belandrino Swerts, Giulia Nicolucci Eleoterio, LIlian Tamy Takahashi, Camila Viale Nogueira, Polianna Rodrigues de Souza, Fernando Moura, Sergio Eduardo Alonso Araujo, Pedro Luiz Serrano Uson Junior, Bernard Lobato Prado
Journal: Journal of Clinical Oncology (2023)

e24168 Background: Prior studies have shown that specialized palliative care (SPC), when integrated early during the disease trajectory, improves the quality of end-of-life care among advanced cancer patients. However, those studies were conducted in large academic cancer centers in developed countries, where the availability of human and structural SPC resources is extensive. Little is known about how the timing of SPC may affect end-of-life quality care indicators in other settings of the globe. We aimed to examine the timing of SPC over a 4-year period and how it was associated with ASCO end-of-life quality care indicators. Methods: Retrospective cohort study of all adult cancer patients referred to the SPC team and who died at Hospital Israelita Albert Einstein, Sao Paulo, Brazil, between April 2017 and April 2021.Data onpatient demographics, clinical characteristics, timing of SPC integration as measured as the median interval between first SPC consult to death (SPC1-D), and ASCO end-of-life quality care indicators were retrieved. Results: Among 292 deceased cancer patients (52% female; median age = 67; 70% ECOG ≥3), the median SPC1-D interval was 24 days. There was a decrease in SPC1-D interval in the pandemic years (April 2017 through March 2018 = 27 days; April 2018 through March 2019 = 39 days; April 2019 through March 2020 = 23 days; April 2020 through April 2021 = 15 days; p = .02). 164 (56%) had an SPC1 &lt; 30 days before death. Patients who had an SPC1 &gt; 30 days before death were less likely to receive chemo and targeted therapy within the last 30 days of life (Table 1). Conclusions: Integration of SPC occurred late, especially during the pandemic years. Nevertheless, earlier SPC1 improved treatment aggressiveness in end-of-life. Further efforts are needed to enhance early SPC referrals in resource-limited settings.[Table: see text]
Reduction in curie score in neuroblastoma patients treated with naxitamab.
Authors: Jaume Mora, Godfrey Chi-Fung Chan, Daniel A. Morgenstern, Loredana Amoroso, Karsten Nysom, Joerg Faber, Arthur Wingerter, Melissa Bear, Alba Rubio-San-Simón, Brian H. Kushner, Karen Tornøe, Rene DePont Christensen
Journal: Journal of Clinical Oncology (2023)

10042 Background: Patients with high-risk neuroblastoma (HR-NB) most frequently present with metastases in the bone marrow (BM; 70–89%) and bone (56–65%). Approximately 15% of HR-NB patients will be refractory to induction therapy and 50% will relapse. Naxitamab is a humanized GD2-binding monoclonal antibody approved in the US with granulocyte-macrophage colony-stimulating factor (GM-CSF) for treatment of patients ≥1-yr with refractory/relapsed (R/R) HR-NB in the bone or BM with partial response, minor response, or stable disease to prior therapy. Curie Score (CS) is an important tool for assessing extent of disease and treatment response. The reduction in CS by baseline disease status, i.e., refractory or relapsed, from Trial 201 pre-specified interim analysis (data cut-off 31-dec-2021) is reported. Methods: Ongoing Trial 201 (phase II, NCT03363373) evaluates naxitamab+GM-CSF in patients with R/R HR-NB with residual disease limited to bone/BM. Soft tissue and actively progressing disease were addressed prior to enrollment. Naxitamab was administered (intravenously) at 3mg/kg/day over 30-60 min on Days 1/3/5 with GM-CSF (subcutaneous) on Days -4 to 5 at 4-week cycles. 123 I-MIBG scans were used to assess CS and treatment response according to INRC criteria per independent review. Results: Interim analysis included 52 (efficacy group) and 74 (safety) patients. The primary endpoint achieved an overall response rate (ORR) of 50% [95% CI: 35.8- 64.2] with complete response rate (CR) of 38%. A summary of changes in overall CS by disease status is reported in the table. Median change in CS from baseline to end of treatment (EOT) was −1 across refractory and relapsed subgroups and ranged from −18 to 18. Baseline CS (≤ 2 vs. ≥3) did not affect the safety profile. The most common adverse events were pain, hypotension, urticaria, and bronchospasm. The frequency of Grade 3 or higher and serious related adverse events was lower for patients with refractory vs. relapsed disease, i.e. lower rates of severe hypotension (51% vs. 68%), increased ALT (0% vs. 14%), and hypoxia (3% vs. 16%). Conclusions: Clinically meaningful reductions in CS were seen in patients regardless of baseline disease status (relapsed or refractory HR-NB). Baseline CS did not affect the safety profile. Refractory patients had a lower frequency of severe and serious related adverse events.. Clinical trial information: NCT03363373 . [Table: see text]
Risk factors and early biomarkers of nephrotoxicity associated with the use of anti-VEGF drugs.
Authors: Katerina Grechukhina, Natalia Chebotareva, Tatyana Krasnova, Lyudmila Zhukova
Journal: Journal of Clinical Oncology (2023)

e24079 Background: Anti-angiogenic anticancer drugs that block VEGF can cause kidney damage (Fujii et al., 2019). Among the mechanisms of nephrotoxicity thrombotic microangiopathy (TMA) of renal vessels can be distinguished (Estrada et al., 2019). TMA can be accompanied the development of anemia, excessive schistocytes, as well as increased LDH levels and a low platelet count, which indicated the occurrence of endothelial dysfunction and microangiopathic processes (Hauser et al, 2009). The goal of this study was to assess the risk factors of early nephrotoxicity and the utility of NGAL, KIM-1, HIF-1α and nephrin levels in urine as early biomarkers of nephrotoxicity. Methods: The study included 50 patients who received anti-VEGF drugs (aflibercept, bevacizumab or ramucirumab). Nephrotoxicity was determined as a decrease in glomerular filtration rate (GFR) to &lt; 60 ml/min/1.73m2 at 8 weeks from the initiation of therapy. The laboratory parameters and the levels of KIM-1, NGAL, HIF-1α and nephrin in urine samples were determined by ELISA before treatment and after 1, 2, 4 and 8 weeks of treatment. To assess risk factors for nephrotoxicity we analyzed primary clinical and laboratory parameters. Results: Nephrotoxicity at 8 weeks was achieved in 21 (42%) of patients. A statistically significant decrease in hemoglobin and platelet count by 20 and 26%, respectively, from the initial level was observed. An increase in the number of schistocytes and a slight increase in LDH levels were also observed. The increase in NGAL, KIM-1 and nephrin levels was statistically significant in 1 weeks and the increase of HIF-1α in 2 weeks after the start of therapy (p = 0.001). The unfavorable predictors of nephrotoxicity as well as the favorable predictors in terms of decreasing renal function are presented in Table. ROC analysis demonstrated high sensitivity and specificity: NGAL – AUC 0.7; KIM-1 – AUC 0.69; HIF-1α – 0.7; nephrin – AUC 0.7. Conclusions: We report a significant increase in the parameters of microangiopathic hemolysis and in urine biomarkers of tubular and podocytic damage as well as hypoxia by the 8th week of treatment. We suggest that the TMA process can take part in renal damage. Increased levels of NGAL, KIM-1, HIF-1α and nephrin in the urine reflect the renal damage processes and have higher sensitivity and specificity then serum creatitine. The independent risk factors for nephrotoxicity are determined. [Table: see text]